Dr Troy Harkness

University of Saskatchewan

Finding new ways to treat drug-resistant cancers

It is often said that you can’t teach an old dog new tricks. But can you teach an old drug new tricks in dogs?

Dr Troy Harkness, a researcher at the University of Saskatchewan in Saskatoon, is studying whether a drug that has been used for decades to treat diabetes can also be used to treat drug-resistant tumours in dogs. The drug, called metformin, has shown promising anticancer activity in laboratory studies, in some cases even killing drug-resistant cancer cells. It is also being actively tested as an experimental treatment for many types of cancer in clinical trials.

With the support of the Canadian Cancer Society, Dr Harkness is the first to study the effect of metformin treatment in dogs who have drug-resistant lymphoma, which is very similar to a type of human blood cancer called non-Hodgkin lymphoma (NHL). In both dogs and humans, lymphomas will often initially respond to chemotherapy, but later develop drug resistance. Since dogs age faster and their cancers advance more rapidly, they can be studied as a model of how human lymphomas may respond to new cancer therapies.

Companion dogs with lymphoma are being recruited from veterinary clinics where they go for treatment. In this study, they will receive standard chemotherapy until they stop responding. Then they will be given metformin in combination with chemotherapy to see if it can reverse the cancer’s drug resistance. By looking at how metformin changes molecular markers associated with drug resistance, Dr Harkness and his colleagues will gain a better understanding of how it can be exploited as new cancer treatment.

A year into the project, Dr Harkness’ team has shown that metformin can reverse molecular markers of drug-resistant lymphoma. If dogs come into the study already displaying the drug resistance markers, they immediately receive metformin in addition to their normal treatment in the hopes of inducing and maintaining prolonged remissions. So far, 2 new dogs have entered the study in this manner and several months later are still in remission.

All of the dogs who have entered the study after failing all available treatments have responded to metformin and shown reversal of the drug resistance markers. One of the dogs went into full remission, accompanied by a complete shrinkage of the tumour that lasted 5 months. Additional dogs will need to be studied to convincingly demonstrate metformin’s anticancer potential.

“Support from the Canadian Cancer Society has been critical for these studies. Without it, we would not know that a potential treatment for drug-resistant cancer – and the potential for detecting it before it becomes clinically evident – was just around the corner,” says Dr Harkness.

New treatment options for people with drug-resistant cancers are sorely needed. If this treatment strategy is successful in dogs, these findings can guide the clinical testing of a similar approach in humans.